[2-[[3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]phenyl]methylamino]-2-oxoethyl] acetate | 586387-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [2-[[3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]phenyl]methylamino]-2-oxoethyl] acetate
• CAS: 586387-88-4
• 化学式: C₂₄H₂₁BrF₂N₂O₅
• 分子量: 535.342
• InChiKey: NSJHIBGKPLJTSB-UHFFFAOYSA-N

物化性质

• 沸点：
  703.9±60.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [2-[[3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]phenyl]methylamino]-2-oxoethyl] acetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 以84%的产率得到N-(3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)benzyl)-2-hydroxyacetamide
  参考文献：
  名称：

  Design, synthesis and activity of a potent, selective series of N -aryl pyridinone inhibitors of p38 kinase

  摘要：

  A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.120
• 作为产物：
  描述：

  1-[3-(chloromethyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one 在 N-甲基吗啉 、 N-溴代丁二酰亚胺(NBS) 、 氨 、 1-羟基苯并三唑 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 28.0h， 生成 [2-[[3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]phenyl]methylamino]-2-oxoethyl] acetate
  参考文献：
  名称：

  Design, synthesis and activity of a potent, selective series of N -aryl pyridinone inhibitors of p38 kinase

  摘要：

  A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.120

文献信息

• Substituted pyridinones
  申请人：Devadas Balekudru

  公开号：US20050176775A1

  公开（公告）日：2005-08-11

  Disclosed are compounds of Formula I and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , and R 5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.

  本发明涉及式I的化合物及其药学上可接受的盐，其中R1、R2、R3、R4和R5在此被定义。这些化合物可用于治疗由未调节的p38 MAP激酶和/或TNF活性引起或加剧的疾病和状况。本发明还涉及含有这些化合物的药物组合物、制备这些化合物的方法以及使用这些化合物的治疗方法。
• SUBSTITUTED PYRIDINONES AS MODULATORS OF P38 MAP KINASE
  申请人：Pharmacia Corporation

  公开号：EP1490064B1

  公开（公告）日：2009-11-18
• US7067540B2
  申请人：——

  公开号：US7067540B2

  公开（公告）日：2006-06-27
• US7629363B2
  申请人：——

  公开号：US7629363B2

  公开（公告）日：2009-12-08